{"title":"Efficacy of Sequential Transarterial Chemoembolization after Stereotactic Body Radiation Therapy versus Radiation Therapy Alone for Recurrent Hepatocellular Carcinoma: A Propensity Score-matched Analysis.","authors":"Jian-Hui Wu, Jun-Qiang Ding, Jing Sun, Wei-Ping He, Xue-Zhang Duan, Wen-Gang Li","doi":"10.14218/JCTH.2025.00568","DOIUrl":"10.14218/JCTH.2025.00568","url":null,"abstract":"<p><strong>Background and aims: </strong>Comparative data on sequential transarterial chemoembolization (TACE) after stereotactic body radiation therapy (SBRT) in recurrent hepatocellular carcinoma (HCC) remain limited. This study aimed to evaluate the efficacy of this combination.</p><p><strong>Methods: </strong>We retrospectively reviewed 152 patients with recurrent HCC who met predefined eligibility criteria; 109 received SBRT alone and 43 received SBRT plus TACE. To minimize selection bias, a 2:1 propensity score matching was performed, resulting in 68 patients in the SBRT-alone group and 36 in the SBRT plus TACE group for the final comparative analysis. Overall survival, progression-free survival, and local control were assessed using the Kaplan-Meier method.</p><p><strong>Results: </strong>The SBRT plus TACE group was associated with numerically higher survival rates, although this difference did not reach statistical significance. The cumulative one-, three-, and five-year overall survival rates were 91.2%, 76.3%, and 61.8% for SBRT alone, compared to 100.0%, 86.1%, and 77.5% for the combination therapy ( <i>p</i> = 0.069). The corresponding progression-free survival rates were 73.1%, 51.1%, and 32.3% versus 88.9%, 58.1%, and 52.3% ( <i>p</i> = 0.091). No acute grade ≥3 toxicities were observed in either group.</p><p><strong>Conclusions: </strong>In this exploratory analysis of recurrent HCC, the combination of SBRT and TACE demonstrated a favorable trend toward improved survival compared with SBRT alone, without an increase in severe toxicity. While these findings did not reach statistical significance, they establish the safety profile of the combined approach and provide preliminary evidence supporting its potential therapeutic role. This hypothesis-generating study justifies and informs the design of larger, prospective trials to definitively evaluate the efficacy of this regimen.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"317-325"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyue Zhao, Feng Xue, Shanshan Wang, Haiyun Ding, Dong Li, Huiying Rao, Fanpu Ji, Jidong Jia, Xiong Ma, Peng Hu, Xiaoguang Dou, Keshu Xu, Shuangqing Gao, Ming Yang, Lai Wei
{"title":"Hypertension Associated with the Risk of Extrahepatic Cancers in the Metabolic Dysfunction-associated Steatotic Liver Disease Population: A Multicenter Cross-sectional Study in China.","authors":"Xinyue Zhao, Feng Xue, Shanshan Wang, Haiyun Ding, Dong Li, Huiying Rao, Fanpu Ji, Jidong Jia, Xiong Ma, Peng Hu, Xiaoguang Dou, Keshu Xu, Shuangqing Gao, Ming Yang, Lai Wei","doi":"10.14218/JCTH.2025.00423","DOIUrl":"10.14218/JCTH.2025.00423","url":null,"abstract":"<p><strong>Background and aims: </strong>Extrahepatic cancers have been recognized as a significant outcome of metabolic dysfunction-associated steatotic liver disease (MASLD), which involves five cardiometabolic risk factors, including hypertension, and is associated with the tumorigenesis of several cancers or with anti-cancer treatment. We aimed to investigate the association between hypertension, liver fibrosis, and extrahepatic cancers in the MASLD population.</p><p><strong>Methods: </strong>This multicenter cross-sectional study was based on a MASLD population from hospital-based databases across 11 centers nationwide in China, according to MASLD diagnostic criteria identified using keywords and ICD-10 codes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between risk factors and extrahepatic cancers.</p><p><strong>Results: </strong>A total of 103,652 individuals with MASLD were identified, among whom 6,605 were diagnosed with extrahepatic cancers. The primary outcome revealed that hypertension was significantly associated with extrahepatic cancers (OR 1.14, 95% CI: 1.08-1.21), and its combination with hyperglycemia further increased this association (OR 1.36, 95% CI: 1.22-1.51). Risk factors for extrahepatic cancers included being over 40 years of age and female sex. Conversely, certain metabolism-based treatments were found to have potentially protective effects, including angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, fibrates, GLP-1 receptor agonists, and thiazolidinediones. After adjusting for confounding factors, the fibrosis-4 (FIB-4) score was associated with extrahepatic cancers. In the hypertension subgroup, FIB-4 scores of 1.30-2.66, 2.67-3.47, and ≥ 3.48 were associated with extrahepatic cancers in individuals aged 35-64 years, consistent with findings in those aged ≥ 65 years of age with FIB-4 ≥ 2.</p><p><strong>Conclusions: </strong>Hypertension combined with liver fibrosis is associated with extrahepatic cancers in patients with MASLD.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"280-290"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term Dynamic Virological Response Patterns and Clinical Outcomes in Hepatitis B Virus-related Cirrhosis: A Real-world 10-year Cohort Study.","authors":"Yuwei Wang, Yaxin Li, Yueyang Yu, Lingna Lyu, Xueying Liang, Yangjie Li, Yanglan He, Yanna Liu, Keke Jin, Chunlei Fan, Yanjing Wu, Shanshan Wang, Steven Dooley, Ying Han, Huiguo Ding","doi":"10.14218/JCTH.2025.00683","DOIUrl":"10.14218/JCTH.2025.00683","url":null,"abstract":"<p><strong>Background and aims: </strong>The long-term clinical outcomes of patients with hepatitis B virus (HBV)-related cirrhosis receiving nucleos(t)ide analog (NA) therapy according to virological response patterns remain inadequately defined. This study aimed to investigate the association between virological response patterns and clinical outcomes in a large, long-term, real-world cohort.</p><p><strong>Methods: </strong>This retrospective-prospective cohort study enrolled patients with HBV-related cirrhosis receiving NA therapy from 2009 to 2019. According to the serum HBV DNA levels during the initial two years of antiviral treatment, patients were categorized as having a complete (CVR) or partial virological response (PVR). Patients with CVR were further stratified according to their dynamic HBV DNA changes during follow-up into maintained virological response (MVR) or virological breakthrough (VBT) patterns. The primary clinical outcomes included hepatocellular carcinoma (HCC), acute-on-chronic liver failure, and liver-related death. Secondary endpoints included recompensation and progression to decompensation. Cox proportional hazards regression was used to assess the association between virological response patterns and clinical endpoints.</p><p><strong>Results: </strong>In total, 1,869 patients were enrolled. During a median follow-up of seven years, the MVR, VBT, and PVR rates were 65.4%, 26.5%, and 8.1%, respectively. The cumulative serum hepatitis B surface antigen (HBsAg) clearance rate was 9.8%. Moreover, 34.9% of patients with HBsAg < 100 IU/mL at baseline experienced HBsAg clearance. Compared with patients with VBT and PVR, those with MVR had a lower five- and ten-year cumulative incidence of HCC in both the compensated (five-year: 10.1% vs. 17.0%; ten-year: 14.2% vs. 33.6%; <i>P</i> < 0.001) and decompensated cirrhosis subgroups (five-year: 19.5% vs. 36.7%; ten-year: 25.7% vs. 49.7%; <i>P</i> < 0.001). Similarly, patients with MVR also had a lower cumulative incidence of liver-related death. Additionally, a higher hepatic recompensation rate was observed in patients with MVR than in those with VBT (34.1% vs. 22.5%, <i>P</i> < 0.001). Importantly, patients achieving HBsAg clearance and undetectable serum HBV DNA levels (\"functional cure\" during ongoing NA therapy) had the lowest five- and ten-year cumulative incidence of HCC (3.9% and 8.7%, respectively).</p><p><strong>Conclusions: </strong>Patients with long-term MVR exhibited a lower incidence of HCC and liver-related death in both compensated and decompensated HBV-related cirrhosis subgroups, especially those achieving \"functional cure.\" However, more than 30% of patients experienced PVR or VBT during long-term NA antiviral therapy. These findings highlight the importance of long-term, rigorous monitoring after initial CVR to optimize outcomes and support clinical decision-making.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"258-268"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Real-world Effectiveness and Safety of Coblopasvir plus Sofosbuvir in the Treatment of Chronic Hepatitis C Infection in Wenzhou, Eastern China: A Multicenter Observational Study.","authors":"Li-Min Ruan, Xiao-Cheng Zhang, Xin-Yu Zhang, Qing-Qing Zhou, Qiong-Na Zheng, Chang-Long Fu, Yi-Bing Hu, Yu Zhou, Yang-He Wu","doi":"10.14218/JCTH.2025.00673","DOIUrl":"10.14218/JCTH.2025.00673","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"358-361"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.","authors":"Xiaoling Su, Aidiya Yimamu, Sheng Tu, Mengxuan Hao, Haiyang Bi, Ting Liu, Minmin Zhang, Xianbin Xu, Xia Yu, Zhenyu Shan, Jifang Sheng, Yu Shi, Zeyu Sun","doi":"10.14218/JCTH.2025.00502","DOIUrl":"10.14218/JCTH.2025.00502","url":null,"abstract":"<p><p>End-stage liver disease (ESLD) is characterized by a dramatic deterioration of liver function, frequently accompanied by systemic inflammatory storms and multiple organ failures. Central to the onset and progression of ESLD, systemic inflammation arises from complex interactions among various inflammatory signaling molecules and immune cells within and beyond the liver. As key inflammatory modulatory molecules, bioactive oxylipins have been increasingly recognized for their complex molecular mechanisms implicated in various diseases. This review aims to summarize recent findings regarding the molecular and immunological mechanisms through which oxylipins contribute to the development of liver injury and failure, with emphasis on both substantial intrahepatic and extrahepatic immune and inflammatory dysregulation associated with ESLD. Furthermore, this review discusses the translational potential of targeting oxylipins for clinical diagnosis, prognosis, and therapeutic intervention in ESLD.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"344-357"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic Dysfunction-associated Steatotic Liver Disease and Chronic Kidney Disease: From Epidemiology and Pathophysiology to Clinical Prediction and Treatment Options.","authors":"Jiacheng Liu, Cuiling Ma, Yafan Wang, Huiying Rao","doi":"10.14218/JCTH.2025.00612","DOIUrl":"10.14218/JCTH.2025.00612","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD) have shown a significant increase in comorbidity on a global scale due to the prevalence of metabolic syndrome. In 2023, a number of academic societies formally proposed the concept of MASLD, superseding the previous terminology of \"non-alcoholic fatty liver disease\" and \"metabolic dysfunction-associated fatty liver disease\". The diagnostic criteria have been revised to place greater emphasis on the association between hepatic steatosis and cardiometabolic risk factors. MASLD constitutes an independent risk factor for CKD, with this risk potentially increasing in line with the severity of fatty degeneration and the progression of hepatic fibrosis. CKD may represent a potential risk factor for the progression of fibrosis in patients with MASLD. The interaction between the two conditions may accelerate the occurrence of cardiovascular events and increase the risk of all-cause mortality. MASLD and CKD may share core pathophysiological mechanisms, including genetic variants, insulin resistance, lipid metabolism disorders, chronic inflammation, oxidative stress, and gut microbiota dysbiosis. However, the bidirectional causal relationship between the two conditions and the molecular dialogue between organs remains unclear. Furthermore, there are significant gaps in clinical prediction tools and targeted treatment strategies for comorbidities. This paper reviews common pathophysiological mechanisms in MASLD and CKD, the epidemiological and clinical evidence linking MASLD to the risk of CKD, biomarkers and clinical prediction models for coexisting conditions, and potential therapeutic strategies. Our aim is to provide a theoretical basis for early identification, mechanism exploration, and clinical treatment of comorbidities.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"326-343"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LDLR<sup>+</sup> Monocytic Myeloid-derived Suppressor Cells Attenuate Allograft Rejection in Liver Transplantation.","authors":"Xin Zhou, Xinqiang Li, Peng Jiang, Shipeng Li, Zhuoyu Jia, Xueteng Wang, Hailun Cai, Huan Liu, Ruidong Ding, Jinzhen Cai","doi":"10.14218/JCTH.2025.00621","DOIUrl":"10.14218/JCTH.2025.00621","url":null,"abstract":"<p><strong>Background and aims: </strong>Liver transplant rejection significantly affects patient prognosis. Myeloid-derived suppressor cells (MDSCs), known for their potent immunoregulatory functions, represent a promising target for managing liver transplant rejection. This study aimed to systematically characterize the diversity of MDSC subsets and their context-dependent functions, particularly within the context of transplant tolerance.</p><p><strong>Methods: </strong>We analyzed clinical and murine liver transplants using single-cell RNA sequencing, bulk RNA sequencing, flow cytometry, multiplex immunohistochemistry, and co-culture assays to phenotype MDSC subsets.</p><p><strong>Results: </strong>Single-cell RNA sequencing analysis of human and murine samples revealed MDSC involvement in transplant rejection. In mice, MDSC scores followed a normal distribution during the first week post-transplant and correlated with clinical flow cytometry data at one month. A distinct LDLR<sup>+</sup> monocytic MDSC (M-MDSC) subset was identified and confirmed through spatial mapping by multiplex immunohistochemistry. Flow cytometry demonstrated dynamic changes in LDLR<sup>+</sup> M-MDSCs across tissues (liver, spleen, peripheral blood, bone marrow, and lymph nodes), with a peak during acute rejection. Co-culture experiments showed that LDLR-/- M-MDSCs exhibited reduced Arg-1/iNOS expression and an impaired capacity to induce inhibitory receptors (TIGIT, PD1, CTLA-4) or suppress effector molecules (GZMB, IFN-γ, IL-2) in CD8<sup>+</sup> T cells.</p><p><strong>Conclusions: </strong>These findings highlight the critical role of MDSCs in liver transplant rejection. LDLR<sup>+</sup> M-MDSCs exhibited enhanced immunosuppressive properties, underscoring their potential clinical relevance in mitigating rejection and promoting immune tolerance.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"301-316"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dengue Viral Infection and Associated Liver Disease.","authors":"Moana Da Silva Santiago, George Y Wu","doi":"10.14218/JCTH.2025.00566","DOIUrl":"10.14218/JCTH.2025.00566","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 3","pages":"362-366"},"PeriodicalIF":6.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yeyu Song, Yameng Liu, Jie Jiang, Youjie Zheng, Zixuan Wang, Cen Xie, Jian-Gao Fan
{"title":"Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk.","authors":"Yeyu Song, Yameng Liu, Jie Jiang, Youjie Zheng, Zixuan Wang, Cen Xie, Jian-Gao Fan","doi":"10.14218/JCTH.2025.00538","DOIUrl":"10.14218/JCTH.2025.00538","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia frequently coexist, yet their causal relationship and underlying mechanisms remain poorly defined. This study aimed to investigate whether a bidirectional causal link exists between MASLD and sarcopenia and to identify the molecular mediators involved in liver-muscle crosstalk.</p><p><strong>Methods: </strong>We applied Mendelian randomization to test the causal effect of sarcopenia-related traits on MASLD risk. To capture distinct clinical features, we established complementary mouse models, including diet-induced and genetic (<i>ob</i>/<i>ob</i>) MASLD models, a stelic animal model, and a drug-induced muscle atrophy model. Multi-tissue transcriptomic profiling was performed on liver and muscle to uncover altered pathways.</p><p><strong>Results: </strong>Complementing prior genetic evidence establishing MASLD as a causal factor for sarcopenia, our Mendelian randomization analysis revealed that diminished muscle mass and muscle function contribute to an elevated risk of MASLD. In mice with MASLD, we observed loss of muscle mass, reduced strength, and ectopic lipid deposition in skeletal muscle. Conversely, muscle atrophy exacerbated hepatic steatosis, inflammation, and fibrosis in MASLD mice. Transcriptional profiling revealed that sarcopenia impairs hepatic metabolic homeostasis by enhancing fatty acid uptake and impairing oxidative phosphorylation, while MASLD, in turn, promotes muscle dysfunction by exacerbating inflammatory responses and metabolic dysfunction. We further identified C-C motif chemokine ligand 2 as a key myokine that drives MASLD, and adrenomedullin as a key hepatokine that triggers sarcopenia.</p><p><strong>Conclusions: </strong>Our findings suggest a potential bidirectional causal relationship between MASLD and sarcopenia, which may be partially mediated by C-C motif chemokine ligand 2 and adrenomedullin.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"121-136"},"PeriodicalIF":6.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk Factors and Biomarkers for Immune Checkpoint Inhibitor-mediated Hepatotoxicity: Emerging Insights and Future Perspectives.","authors":"Zaoqin Yu, Yanjiao Xu, Wei Li, Yingjie Hu, Chengliang Zhang","doi":"10.14218/JCTH.2025.00622","DOIUrl":"10.14218/JCTH.2025.00622","url":null,"abstract":"<p><p>In the past decade, immune checkpoint inhibitors (ICIs) have dramatically changed cancer treatment, significantly improving outcomes for patients with various malignancies. Nonetheless, their widespread application has resulted in a rise in immune-related adverse events due to excessive immune activation, including immune-mediated hepatotoxicity (IMH). IMH can cause serious complications and even death, underscoring the need for early prediction and intervention. This review outlines the current understanding of risk factors and predictive biomarkers for IMH in cancer patients undergoing ICI therapy, with risk factors divided into patient-associated, tumor-associated, and agent-associated categories. Higher IMH risk is related to female sex, younger age, extreme BMI, Asian ethnicity, and chronic liver disease. Cancer type, prior ICI treatment, dual ICI combination therapy, and the concurrent use of chemotherapy, targeted agents, or other hepatotoxic drugs (e.g., acetaminophen, statins) also increase the risk of IMH. Potential predictive biomarkers encompass circulating blood cells, serum proteins, autoantibodies, cytokines, gene profiles, and the gut microbiome. Despite promising findings, the predictive value of these biomarkers remains inconsistent, and no definitive biomarker has been established for routine clinical use. Large-scale prospective studies are essential to verify the predictive value of these biomarkers and facilitate their integration into clinical practice, thereby providing deeper insights into the early identification and individualized management of IMH during ICI therapy.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 2","pages":"215-231"},"PeriodicalIF":6.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}